Dysfunctional uterine bleeding is a common clinical problem in gynecology. Any woman may be affected during reproductive and later years. Dysfunctional bleeding is characterized by menorrhagia (excessive cyclical bleeding, greater than or equal to 80 ml/cycle) (Gleesen et al., Eur J Obstet Gynecol Reprod Biol, 48(3), 207-214 (1993)), metrorrhagia (abnormal frequency of cycles), bleeding in addition to normal cycles, or bleeding without normal cycles.
Potential causes of abnormal bleeding are numerous, and include physiological transition (e.g. menopause), pregnancy, endometrial cancer, or fibromyomata, and thus the diagnosis of dysfunctional uterine bleeding must be made after careful investigation to exclude these other causes (Galle et al., Postarad Med, 93(2), 73-76 (1993)).
In most cases, dysfunctional uterine bleeding is associated with anovulation (Bayer et al., JAMA, 269(14), 1823-1828 (1993)). Anovulatory bleeding is frequent in pubertal and perimenopausal phases, and is physiological, probably related to changing estrogen levels (Id.). However, bleeding may be caused by chronic anovulation secondary to unopposed estrogen secretion which causes endometrial proliferation, and is associated with increased risk of endometrial cancer (Id.). Inappropriate estrogen levels, either excess estrogen or estrogen unopposed by appropriate progestagen (progesterone) levels, are considered the likely cause of many cases of dysfunctional uterine bleeding.
Treatment of anovulatory bleeding is designed generally to reduce bleeding, and more particularly to halt acute bleeding, prevent recurrence of bleeding, and prevent long-term complications (Id.). First treatment approaches are medical, and the areas and limitations of options available are tabulated.
______________________________________ THERAPY OBJECTIVE(S) Limitation(s) ______________________________________ 1) GnRH Blocks estrogen .cndot. By injection Agonists.sup.1 secretion at .cndot. Accelerates pituitary axis osteoporosis level .cndot. Limited to preoperative use .cndot. Side effects 2) Cyclical Corrects estrogen .cndot. Limited Oral progestagen effectiveness Progestagens.sup.2,3 ratio .cndot. Side effects 3) Nonsteroidal Local endo- .cndot. Limited Anti-inflammatory metrial actions effectiveness Agents .cndot. Non-specific agent .cndot. Side effects ______________________________________ .sup.1 Thomas et al., Br J Obstet Gynaecol, 98(11), 1155-1159 (1991). .sup.2 Fraser, Aust NZ J Obstet Gynaecol, 30(4), 353-356 (1990). .sup.3 Bonduelle, Postgrad Med J, 67(791), 833-836 (1991).
When these therapies fail, surgery is usually indicated. Such surgery is usually either endometrial ablation or hysterectomy, but these procedures are associated with significant costs and side effects, (Thomas et al., supra,; Perino, Acta Eur Perti, 21(6), 313-317 (1990)) some with a failure rate up to 20% (Fraser, supra.; Hellen, Histopathology, 22 (4), 361-365 (1993)) . A significant portion of the 500,00 hysterectomies performed annually in the USA are to treat dystunctional uterine bleeding (Perino, Supra.)